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Information on EC 1.8.4.12 - peptide-methionine (R)-S-oxide reductase and Organism(s) Mus musculus and UniProt Accession Q78J03

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IUBMB Comments
The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for reduction of the R-form of methionine S-oxide, with higher activity being observed with L-methionine S-oxide than with D-methionine S-oxide . While both free and protein-bound methionine (R)-S-oxide act as substrates, the activity with the peptide-bound form is far greater . The enzyme plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. In some species, e.g. Neisseria meningitidis, both this enzyme and EC 1.8.4.11, peptide-methionine (S)-S-oxide reductase, are found within the same protein whereas in other species, they are separate proteins [3,5]. The reaction proceeds via a sulfenic-acid intermediate [5,10]. For MsrB2 and MsrB3, thioredoxin is a poor reducing agent but thionein works well . The enzyme from some species contains selenocysteine and Zn2+.
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Mus musculus
UNIPROT: Q78J03
Word Map
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The taxonomic range for the selected organisms is: Mus musculus
Synonyms
1-Cys methionine sulfoxide reductase B, 1-Cys MSRB, CBS-1, CBS1, cysteine-containing methionine-R-sulfoxide reductase, LOC100305558, LOC100798757, methionine sulfoxide reductase, methionine sulfoxide reductase B, methionine sulfoxide reductase B1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cysteine-containing methionine-R-sulfoxide reductase
244
-
methionine sulfoxide reductase
244
-
methionine sulfoxide reductase B
244
-
methionine sulfoxide reductase B1
methionine sulfoxide reductase B2
284366
-
methionine sulfoxide reductases B
284366
-
methionine-R-sulfoxide reductase
244
-
methionine-R-sulfoxide reductase B2
284366
-
MSRB1
MsrB3
284369
-
Sel-X
244
-
selenocysteine-containing methionine-R-sulfoxide reductase
244
-
selenoprotein R
244
-
SelR
244
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-methionine (R)-sulfoxide + thioredoxin = L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
selenomethionine is essential for MsrB activity
-
peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (R)-S-oxide + thioredoxin
show the reaction diagram
catalytic mechanism involving residues at positions 95, 41, 97, 77, and 80, molecular modeling, role of selenocysteine- and cysteine residues in catalysis, overview
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
peptide-methionine:thioredoxin-disulfide S-oxidoreductase [methionine (R)-S-oxide-forming]
The reaction occurs in the reverse direction to that shown above. The enzyme exhibits high specificity for reduction of the R-form of methionine S-oxide, with higher activity being observed with L-methionine S-oxide than with D-methionine S-oxide [9]. While both free and protein-bound methionine (R)-S-oxide act as substrates, the activity with the peptide-bound form is far greater [10]. The enzyme plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. In some species, e.g. Neisseria meningitidis, both this enzyme and EC 1.8.4.11, peptide-methionine (S)-S-oxide reductase, are found within the same protein whereas in other species, they are separate proteins [3,5]. The reaction proceeds via a sulfenic-acid intermediate [5,10]. For MsrB2 and MsrB3, thioredoxin is a poor reducing agent but thionein works well [11]. The enzyme from some species contains selenocysteine and Zn2+.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
dabsyl L-methionine (R)-sulfoxide + thioredoxin
dabsyl L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
cytosolic human thioredoxin 1, mitochondrial rat thioredoxin 2 lacking a mitochondrial signal peptide or Escherichia coli thioredoxin
-
-
?
dabsyl-L-methionine (R)-sulfoxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
dabsyl-L-methionine-(R)-S-oxide + dithiothreitol
dabsyl-L-methionine + DTT disulfide + H2O
show the reaction diagram
-
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
protein-L-methionine (R)-S-oxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
Met sulfoxide residues in an Met-rich proteins can be reduced by MsrA and MsrB
-
-
?
dabsyl-L-methionine (R)-sulfoxide + 1,4-dithioerythritol
dabsyl-L-methionine + 1,4-dithioerythritol disulfide + H2O
show the reaction diagram
-
-
-
-
?
dabsyl-L-methionine (R)-sulfoxide + dithiothreitol
dabsyl-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
dabsyl-L-methionine (R)-sulfoxide + thioredoxin
dabsyl-L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine-(R)-S-oxide + DTT
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
isozymes MsrB1, MsrB2, and MsrB3
-
-
?
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
protein-L-methionine (R)-S-oxide + dithiothreitol
protein-L-methionine + dithiothreitol disulfide + H2O
show the reaction diagram
Q78J03
Met sulfoxide residues in an Met-rich proteins can be reduced by MsrA and MsrB
-
-
?
L-methionine (R)-sulfoxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
L-methionine-(R)-S-oxide + thioredoxin
L-methionine + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
thioredoxin
-
-
dithiothreitol
-
results in higher activity compared to cofactor thioredoxin
thioredoxin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
-
contains zinc
selenium
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-Methionine sulfone
-
-
additional information
-
selenium-adequate diet retains MsrB mRNA and protein expression at basal levels
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03 - 0.05
dithiothreitol
0.66 - 7
thioredoxin
0.31 - 1.3
L-methionine-(R)-S-oxide
additional information
additional information
-
thioredoxin- and DTT-dependent kinetics of wild-type and mutant enzymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 0.46
L-methionine-(R)-S-oxide
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.023
-
in 100 mM sodium phosphate, at 37°C and pH 5.7
0.055
-
in 100 mM sodium phosphate, at 37°C and pH 6.5
0.074
-
in 50 mM carbonate-bicarbonate, at 37°C and pH 10.0
0.106
substrate: cytosolic human thioredoxin 1
0.11
-
in 100 mM sodium phosphate, at 37°C and pH 7.0
0.119
-
in 50 mM Tris-HCl, at 37°C and pH 7.6
0.128
substrate: mitochondrial rat thioredoxin 2 lacking a mitochondrial signal peptid
0.142
substrate: Escherichia coli thioredoxin
0.228
-
in 100 mM sodium phosphate, at 37°C and pH 7.5
0.267
-
in 50 mM Tris-HCl, at 37°C and pH 8.0
0.272
-
in 50 mM carbonate-bicarbonate, at 37°C and pH 9.6
0.291
substrate: dithiothreitol
0.446
-
in 50 mM Tris-HCl, at 37°C and pH 8.6
0.462
-
in 50 mM carbonate-bicarbonate, at 37°C and pH 9.2
0.484
-
in 50 mM Tris-HCl, at 37°C and pH 9.0
0.000046
-
purified recombinant wild-type cysteine-containing isozyme MsrB1 expressed in NIH 3T3 cells, substrates are L-methionine-(R)-S-oxide and thioredoxin
0.0007
-
kidney, substrate L-methionine (R)-sulfoxide
0.0019
-
liver, substrate L-methionine (R)-sulfoxide
0.002
-
purified recombinant wild-type cysteine-containing isozyme MsrB1 expressed in NIH 3T3 cells, substrates are L-methionine-(R)-S-oxide and DTT
0.01
-
purified recombinant wild-type isozyme MsrB2 expressed in Escherichia coli, substrates are L-methionine-(R)-S-oxide and thioredoxin
0.045
-
purified recombinant wild-type selenocysteine-containing isozyme MsrB1 expressed in NIH 3T3 cells, substrates are L-methionine-(R)-S-oxide and thioredoxin
0.17
-
purified recombinant wild-type selenocysteine-containing isozyme MsrB1 expressed in NIH 3T3 cells, substrates are L-methionine-(R)-S-oxide and DTT
0.386
-
purified recombinant wild-type isozyme MsrB2 expressed in Escherichia coli, substrates are L-methionine-(R)-S-oxide and DTT
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
MSRB2_MOUSE
175
0
19157
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5000
-
MsrB1 occurs in two protein forms that migrate as 14000 and 5000 Da proteins, SDS-PAGE
13000
-
x * 13000, native wild-type MsrB, SDS-PAGE
14000
-
MsrB1 occurs in two protein forms that migrate as 14000 and 5000 Da proteins, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 13000, native wild-type MsrB, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C98S
-
the mutant show increased Km values with dithiothreitol (1.7fold) and thioredoxin (6fold) compared to the wild type enzyme
E81V
-
site-directed mutagenesis, mutation in the selenocysteine-containing or the cysteine-containing isozyme MsrB1, both mutants show reduced activity with either cofactor thioredoxin and DTT compared to wild-type MsrB1s
F97N
-
site-directed mutagenesis, mutation in the selenocysteine-containing or the cysteine-containing isozyme MsrB1, both mutants show altered activity and kinetics compared to wild-type MsrB1s
G77H
-
site-directed mutagenesis, mutation in the selenocysteine-containing or the cysteine-containing isozyme MsrB1, the selenocysteine-containing mutant shows reduced activity with either cofactor thioredoxin and DTT compared to wild-type selenocysteine MsrB1, while the cysteine-containing mutant shows activity and kinetics similar to the wild-type cysteine MsrB1
G77H/E81V/F97N
-
site-directed mutagenesis, mutation in the selenocysteine-containing or the cysteine-containing isozyme MsrB1, both mutants show altered activity and kinetics compared to wild-type MsrB1s
G77H/F97N
-
site-directed mutagenesis, mutation in the selenocysteine-containing or the cysteine-containing isozyme MsrB1, both mutants show altered activity and kinetics compared to wild-type MsrB1s
H77G
-
site-directed mutagenesis, mutation of isozyme MsrB2 leads to highly reduced activity with either cofactor thioredoxin and DTT compared to wild-type MsrB2
H77G/N97F
-
site-directed mutagenesis, mutation of isozyme MsrB2, inactive mutant
H77G/V81E/N97F
-
site-directed mutagenesis, mutation of isozyme MsrB2, inactive mutant
N97F
-
site-directed mutagenesis, mutation of isozyme MsrB2, the mutant is inactive with cofactor thioredoxin and shows highly reduced activity with cofactor DTT compared to wild-type MsrB2
N97Y
-
site-directed mutagenesis, mutation of isozyme MsrB2, the mutant is inactive with cofactor thioredoxin and shows highly reduced activity with cofactor DTT compared to wild-type MsrB2
U95C
-
the mutant has a significantly decreased activity
V81E
-
site-directed mutagenesis, mutation of isozyme MsrB2 leads to reduced activity with either cofactor thioredoxin and DTT compared to wild-type MsrB2
additional information
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography, and gel filtration
-
partial purification of native MsrB from liver, recombinant modified MsrB from Escherichia coli
-
recombinant C-terminally His-tagged wild-type and mutant MsrB to homogeneity
-
recombinant wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by heparin affinity chromatography
-
recombinant wild-type and mutant isozymes MsrB1 and MsrB2 from Escherichia coli strain BL21(DE3) and NIH-3T3 cells
-
Talon Co2+ affinity resin column chromatography
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
MsrB2DELTAS containing one extra amino acid in N-terminal (Met) and a C-terminal His-tag is expressed in Escherichia coli
-
co-expressed with transient receptor potential melastatin type 6 in HEK-293 cells
-
endoplasmic reticulum isozyme MsrB3, DNA and amino acid sequence determination and analysis, expression of different constructs of GFP-tagged MsrB3 in monkey kidney CV-1 cells or in mouse fibroblast NIH 3T3 cells
expressed in Escherichia coli BL21(DE3) and in HEK-293 cells
-
expressed in Escherichia coli ER2566 cells
-
expression of wild-type and mutant isozymes MsrB1 and MsrB2 in Escherichia coli strain BL21(DE3) and in NIH-3T3 cells
-
gene msrB with the codon for selenomehinonine is exchanged for methionine, overexpression in Escherichia coli
-
overexpression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
overexpression of wild-type and mutants in Escherichia coli, expression as N- or C-terminally 6His-tagged protein lowers the recombinant expression level to 3% of total enzyme expressed, labeling of expressed wild-type with 75SeMet
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kryukov, G.V.; Kumar, R.A.; Koc, A.; Sun, Z.; Gladyshev, V.N.
Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase
Proc. Natl. Acad. Sci. USA
99
4245-4250
2002
Drosophila melanogaster (Q8INK9), Mus musculus
Manually annotated by BRENDA team
Moskovitz, J.; Singh, V.K.; Requena, J.; Wilkinson, B.J.; Jayaswal, R.K.; Stadtman, E.R.
Purification and characterization of methionine sulfoxide reductases from mouse and Staphylococcus aureus and their substrate stereospecificity
Biochem. Biophys. Res. Commun.
290
62-65
2002
Mus musculus, Staphylococcus aureus
Manually annotated by BRENDA team
Bar-Noy, S.; Moskovitz, J.
Mouse methionine sulfoxide reductase B: effect of selenocysteine incorporation on its activity and expression of the seleno-containing enzyme in bacterial and mammalian cells
Biochem. Biophys. Res. Commun.
297
956-961
2002
Mus musculus
Manually annotated by BRENDA team
Weissbach, H.; Resnick, L.; Brot, N.
Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage
Biochim. Biophys. Acta
1703
203-212
2005
Bos taurus, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Homo sapiens, Mus musculus, Neisseria gonorrhoeae, Neisseria meningitidis, Saccharomyces cerevisiae, Streptococcus gordonii (Q9LAM9), Streptococcus gordonii, Streptococcus pneumoniae
Manually annotated by BRENDA team
Moskovitz, J.
Methionine sulfoxide reductases: ubiquitous enzymes involved in antioxidant defense, protein regulation, and prevention of aging-associated diseases
Biochim. Biophys. Acta
1703
213-219
2005
Arabidopsis thaliana, Escherichia coli, Homo sapiens, Mus musculus, Saccharomyces cerevisiae, Staphylococcus aureus, Sus scrofa
Manually annotated by BRENDA team
Stadtman, E.R.; Moskovitz, J.; Berlett, B.S.; Levine, R.L.
Cyclic axidation and reduction of protein methionine residues is an important antioxidant mechanism
Mol. Cell. Biochem.
2347235
3-9
2002
Mus musculus
-
Manually annotated by BRENDA team
Kim, H.Y.; Gladyshev, V.N.
Characterization of mouse endoplasmic reticulum methionine-R-sulfoxide reductase
Biochem. Biophys. Res. Commun.
320
1277-1283
2004
Mus musculus, Mus musculus (Q8BU85)
Manually annotated by BRENDA team
Moskovitz, J.
Roles of methionine suldfoxide reductases in antioxidant defense, protein regulation and survival
Curr. Pharm. Des.
11
1451-1457
2005
Arabidopsis thaliana, Homo sapiens, Mus musculus, Saccharomyces cerevisiae
Manually annotated by BRENDA team
Kim, H.Y.; Gladyshev, V.N.
Different catalytic mechanisms in mammalian selenocysteine- and cysteine-containing methionine-R-sulfoxide reductases
PLoS Biol.
3
2080-2089
2005
Homo sapiens, Mus musculus
-
Manually annotated by BRENDA team
Kim, H.Y.; Kim, J.R.
Thioredoxin as a reducing agent for mammalian methionine sulfoxide reductases B lacking resolving cysteine
Biochem. Biophys. Res. Commun.
371
490-494
2008
Homo sapiens (Q8IXL7), Mus musculus (Q78J03)
Manually annotated by BRENDA team
Kim, H.Y.; Gladyshev, V.N.
Methionine sulfoxide reductases: selenoprotein forms and roles in antioxidant protein repair in mammals
Biochem. J.
407
321-329
2007
Bacillus subtilis (P54155), Drosophila melanogaster, Homo sapiens (Q8IXL7), Mus musculus (Q8BU85), Neisseria meningitidis
Manually annotated by BRENDA team
Le, D.T.; Liang, X.; Fomenko, D.E.; Raza, A.S.; Chong, C.K.; Carlson, B.A.; Hatfield, D.L.; Gladyshev, V.N.
Analysis of methionine/selenomethionine oxidation and methionine sulfoxide reductase function using methionine-rich proteins and antibodies against their oxidized forms
Biochemistry
47
6685-6694
2008
Mus musculus (Q78J03)
Manually annotated by BRENDA team
Uthus, E.O.; Moskovitz, J.
Specific activity of methionine sulfoxide reductase in CD-1 mice is significantly affected by dietary selenium but not zinc
Biol. Trace Elem. Res.
115
265-276
2007
Mus musculus
Manually annotated by BRENDA team
Breivik, A.S.; Aachmann, F.L.; Sal, L.S.; Kim, H.Y.; Del Conte, R.; del Conte, R.; Gladyshev, V.N.; Dikiy, A.
1H, 15N and 13C NMR assignments of mouse methionine sulfoxide reductase B2
Biomol. NMR Assign.
2
199-201
2008
Mus musculus, Mus musculus (Q78J03)
Manually annotated by BRENDA team
Uthus, E.O.
Determination of the specific activities of methionine sulfoxide reductase A and B by capillary electrophoresis
Anal. Biochem.
401
68-73
2010
Mus musculus
Manually annotated by BRENDA team
Cao, G.; Lee, K.P.; van der Wijst, J.; de Graaf, M.; van der Kemp, A.; Bindels, R.J.; Hoenderop, J.G.
Methionine sulfoxide reductase B1 (MsrB1) recovers TRPM6 channel activity during oxidative stress
J. Biol. Chem.
285
26081-26087
2010
Mus musculus
Manually annotated by BRENDA team
Aachmann, F.L.; Sal, L.S.; Kim, H.Y.; Marino, S.M.; Gladyshev, V.N.; Dikiy, A.
Insights into function, catalytic mechanism, and fold evolution of selenoprotein methionine sulfoxide reductase B1 through structural analysis
J. Biol. Chem.
285
33315-33323
2010
Mus musculus (Q9JLC3)
Manually annotated by BRENDA team
Liang, X.; Fomenko, D.E.; Hua, D.; Kaya, A.; Gladyshev, V.N.
Diversity of protein and mRNA forms of mammalian methionine sulfoxide reductase B1 due to intronization and protein processing
PLoS ONE
5
e11497
2010
Mus musculus
Manually annotated by BRENDA team
Dobrovolska, O.; Rychkov, G.; Shumilina, E.; Nerinovski, K.; Schmidt, A.; Shabalin, K.; Yakimov, A.; Dikiy, A.
Structural insights into interaction between mammalian methionine sulfoxide reductase B1 and thioredoxin
J. Biomed. Biotechnol.
2012
586539
2012
Mus musculus (Q9JLC3)
Manually annotated by BRENDA team
Aachmann, F.L.; Kwak, G.H.; Del Conte, R.; Kim, H.Y.; Gladyshev, V.N.; Dikiy, A.
Structural and biochemical analysis of mammalian methionine sulfoxide reductase B2
Proteins
79
3123-3131
2011
Mus musculus, Mus musculus (Q78J03)
Manually annotated by BRENDA team
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